Biology Reference
In-Depth Information
infect humans (
Beier, 1998
)). If the mosquito subsequently takes another
blood meal, these infectious sporozoites will be inoculated into the subcu-
taneous tissue, thus initiating a new human
P. vivax
infection.
In
P. vivax
,
Plasmodium ovale
and
Plasmodium malariae
infections, a pro-
portion of erythrocytic merozoites will begin replicating sexually to
produce male and female offspring immediately after release from the liver.
In clinical trials of
P. vivax
therapy, the proportion of patients who are game-
tocytaemic on enrolment typically varies from 60 to 95% (
Huh et al., 2011
;
Ratcliff et al., 2007
;
Hasugian et al., 2007
). By contrast, gametocytogen-
esis in
P. falciparum
infections is delayed by 1 or 2 weeks with respect to
the initiation of blood-stage asexual parasite replication (
Stepniewska et al.,
2008
). Consequently,
P. vivax
, but not
P. falciparum
infections, are usually
transmissible before symptom onset, and thus before anti-malarial treatment
is commenced.
The defining feature of
P. vivax
malaria, and one that plays an important
part in its refractoriness to current malaria control strategies, is its abil-
ity to relapse from dormant liver forms. After arrival in the human liver,
an unknown, and probably variable, proportion of sporozoites differentiate
to become dormant hypnozoites. These inert forms reawaken at intervals
following the initial bout of malaria giving rise to recurrent blood-stage
infections. The frequency and pattern of these relapses vary widely by
geographic region, and even within the same locale, ranging from three
weekly relapses in many equatorial regions to relapse intervals of 6 months
or greater in many temperate regions (
Hill and Amatuzio, 1949
;
Coatney
et al., 1950
;
Hankey et al., 1953
). Biphasic relapse patterns characterised by
long periods of latency followed by a burst of frequent relapses have also
been described and some strains do not cause a primary blood-stage infec-
tion at all (
Hankey et al., 1953
). The determinants of the periodicity of these
relapses are unclear but one leading hypothesis is that febrile malaria episodes
'reawaken' dormant hypnozoites in a self-fulfilling cycle (see Chapter 2)
(
White, 2011
;
Douglas et al., 2011
;
Looareesuwan et al., 1987
). The duration
over which relapses from a single inoculation occur is not entirely clear but
induced infections with the Chesson strain, prevalent in the island of New
Guinea, have been shown to relapse for up to 5 years following initial inoc-
ulation (provided the development of homologous immunity is limited by
prompt blood schizontocidal treatment of each relapse) (
Hill and Amatuzio,
1949
). In the absence of anti-malarial treatment, non-immune adults will
develop clinical tolerance to persistent
P. vivax
parasitaemia in the space of
3-8 weeks (
Boyd, 1938
). Homologous immunity strong enough to suppress
